Buck C, Digel W, Schöniger W, Stefanic M, Ragnavachar A, Heimpel H, Porzsolt F
Department of Medicine III (Hematology/Oncology), University of Ulm, F.R.G.
Leukemia. 1990 Jun;4(6):431-4.
We investigated the effect of recombinant tumor necrosis factor-alpha (rTNF-alpha) and recombinant lymphotoxin (rLT) in the growth modulation of purified hairy cell leukemia (HCL) cells. In response to rTNF-alpha, HCL cells from five of eight patients showed a 3 to 23-fold thymidine incorporation above their unstimulated controls. The effect was time and dose dependent with a maximum between 10 and 25 ng/ml rTNF-alpha after 120-hr incubation. rLT (1-50 ng/ml), however, could not enhance DNA synthesis in six of six cases. Cell number of rTNF-alpha stimulated cells ranged from 2-3 x 10(6)/ml from days 0-50 whereas cell number of unstimulated controls decreased from 3 x 10(6)/ml at day 0 to 0.01-0.02 x 10(6)/ml after 50 days in culture. rTNF-alpha induced proliferation could be suppressed in all HCL cell populations by 0.3 ng/ml recombinant interferon alpha (100 U/ml rIFN-alpha). TNF binding studies in two patients revealed that both TNF-sensitive HCL cells (1,990 +/- 148 receptors/cell) as well as TNF-insensitive HCL cells (1,261 +/- 101 receptors/cell) express specific receptors for TNF-alpha. These data show that rTNF-alpha and rLT have different effects on the growth of HCL cells. In addition there is a subgroup of patients who show no response to rLT or rTNF-alpha.
我们研究了重组肿瘤坏死因子-α（rTNF-α）和重组淋巴毒素（rLT）对纯化的毛细胞白血病（HCL）细胞生长调节的影响。在rTNF-α作用下，8例患者中有5例的HCL细胞显示，其胸苷掺入量比未刺激的对照高出3至23倍。该效应具有时间和剂量依赖性，在120小时孵育后，10至25 ng/ml的rTNF-α作用下达到最大值。然而，在6例患者中，rLT（1 - 50 ng/ml）均不能增强DNA合成。rTNF-α刺激的细胞在第0至50天的细胞数量范围为2 - 3×10⁶/ml，而未刺激的对照细胞数量在培养50天后从第0天的3×10⁶/ml降至0.01 - 0.02×10⁶/ml。0.3 ng/ml的重组干扰素α（100 U/ml rIFN-α）可抑制所有HCL细胞群体中rTNF-α诱导的增殖。对两名患者的TNF结合研究表明，TNF敏感的HCL细胞（1990±148个受体/细胞）以及TNF不敏感的HCL细胞（1261±101个受体/细胞）均表达TNF-α的特异性受体。这些数据表明，rTNF-α和rLT对HCL细胞的生长具有不同影响。此外，有一小部分患者对rLT或rTNF-α无反应。
